Malaria remains a serious global health problem for which there is no effective vaccine. Previous studies indicate that animals can be immunized with inactivated sporozoites. The gene coding for the circumsporozoite (CSP) antigen of the malaria parasite Plasmodium falciparum was inserted into the vaccinia virus genome under the control of a defined vaccinia virus promoter. Tissue culture cells infected with the recombinant synthesized polypeptides that reacted with monoclonal antibody against the malaria protein. Studies on the sequence of the expressed P. falciparum CSP indicated that the NH2-terminus is blocked and COOH-terminus is not processed. Immunofluorescent staining demonstrated that the CSP was distributed primarily in the cytoplasm of infected cells. Mice and rabbits vaccinated with the recombinant virus produced antibodies that bound specifically to sporozoites. The S-antigen gene of P. falciparum also was expressed in a vaccinia virus recombinant. The protein was secreted from infected cells and reacted with specific antiserum. Vaccinated animals produces a low but detectable antibody response. By attaching the transmembrane domain of an immunoglobulin gene to the S-antigen gene, a new form of the plasmodial protein was synthesized. This chimeric protein was no longer secreted but became attached to the plasma membrane. Significantly, rabbits immunized with the new recombinant vaccinia virus developed much higher antibody levels to S-antigens.